Besides its centerfold, a major part of Playboy for much of its existence has been the Playboy Interview, an extensive (usually several thousand-word) discussion between a notable individual and an interviewer (historian Alex Haley, for example, served as a Playboy interviewer on a few occasions; one of his interviews was with Martin Luther King Jr.; he also interviewed Malcolm X, then coauthored his autobiography). One of the magazine's most notable interviews was a discussion with then-presidential candidate Jimmy Carter in the November 1976 issue in which he stated "I've committed adultery in my heart many times."[28][29]David Sheff's interview with John Lennon and Yoko Ono appeared in the January 1981 issue, which was on newsstands at the time of Lennon's murder; the interview was later published in book format.

Another interview type section, entitled "20Q" (a play on the game of Twenty Questions), was added in October 1978. Cheryl Tiegs was the first interviewee for the section.[30]